PROFIL FARMAKOKINETIK OKSITETRASIKLIN PADA IKAN LELE, Clarias gariepinus DENGAN INFEKSI ARTIFISIAL Aeromonas hydrophila
Abstract
Oksitetrasiklin banyak digunakan dalam manajemen terapeutik maupun preventif infeksi penyakit bakterial pada akuakultur. Konsentrasi obat yang tepat dalam tubuh penting untuk kemanjuran terapi tidak hanya ditentukan oleh dosis obat tetapi juga farmakokinetik obat yang dapat diketahui dari parameter farmakokinetiknya. Parameter farmakokinetik meliputi waktu paruh, kadar puncak, waktu puncak, volume distribusi, area di bawah kurva (AUC), eliminasi, dan distribusi obat baik dalam keadaan fisiologi maupun patologi. Penelitian ini bertujuan untuk mengetahui parameter farmakokinetik dan waktu henti obat (withdrawal time) oksitetrasiklin yang diberikan secara oral pada ikan lele yang diinfeksi dengan Aeromonas hydrophila. Kondisi patofisiologi yang memengaruhi mekanisme kerja obat akibat infeksi A. hydrophila diketahui dengan pengamatan histologi. Visualisasi keberadaan bakteri A. hydrophila pada organ ikan lele menggunakan imunohistokimia. Konsentrasi obat dalam plasma diukur dengan kromatografi cair kinerja tinggi (KCKT). Studi ini mengungkapkan farmakokinetik obat dan waktu henti obat yang berbeda pada ikan sehat/tidak diinfeksi dan sakit/diinfeksi A. hydrophila. Kadar oksitetrasiklin pada plasma ikan sehat 229,00 mg/L dan ikan terinfeksi A. hydrophila 99,16 mg/L yang dicapai pada 1,5 jam setelah pemberian. Area di bawah kurva yang menggambarkan jumlah obat dalam sirkulasi sistemik pada ikan sehat sebesar 943,6 mg.h/L; sedangkan pada ikan sakit sebesar 814,05 mg.h/L. Area di bawah kurva untuk waktu tak terhingga pada ikan sehat 1.586,42 mg.h/L dan 1.516,47 mg.h/L. Waktu paruh pada ikan sehat 9,36 jam dan ikan tidak terinfeksi 9,65 jam. Pengamatan histologi pada organ yang berperan dalam mekanisme obat yaitu hati, ginjal, dan usus mengalami kelainan patologi. Visualisasi A. hydrophila dengan imunohistokimia menunjukkan bakteri banyak terlokasilasi dalam lumen pembuluh darah. Waktu henti obat setelah 10 hari pemberian dengan dosis terapeutik pada ikan sehat yaitu 20 hari pada ikan sehat dan 30 hari pada ikan sakit. Sebagai kesimpulan kadar oksitetrasiklin pada plasma ikan sehat lebih besar daripada ikan sakit, dan diikuti dengan perbedaan pada parameter farmakokinetik lainnya dan waktu henti obat yang lebih lama pada ikan sakit.
Oxytetracycline is widely used in the therapeutic and preventive management of bacterial infections in aquaculture. The accurate concentration of drug in the body is important for therapeutic efficacy not only determined by the dose but also the pharmacokinetics of the drug which can be known from its pharmacokinetic parameters. Pharmacokinetic parameters include half-life, maximum concentration, time of maximum concretation, volume distribution, area under the curve (AUC), elimination, and distribution of the drug in both physiological and pathological conditions. This study aimed to determine the pharmacokinetic parameters and withdrawal time of oxytetracycline administered orally to uninfected and infected catfish infected with Aeromonas hydrophila. Pathophysiological conditions that affect the drug’s mechanism of action due to infection with A. hydrophila by histological observations. Visualization of A. hydrophila bacteria in catfish organs using immunohistochemical assay. The plasma drug concentration was measured by high performance liquid chromatography (HPLC). This study revealed different drug pharmacokinetics parameters and withdrawl time of uninfected and infected fish with A. hydrophila. Oxytetracycline levels in the plasma of the uninfected fish were 229.00 mg/L and 99.16 mg/L in infected fish which were reached 1.5 hours after administration. The area under the curve that describes the amount of drug in the systemic circulation of uninfected fish is 943.6 mg.h/L, while in infected fish is 814.05 mg.h/L. The area under the curve for infinitive depicting the amount of drug in the systemic circulation in uninfected fish was 943.6 mg.h/L, while in infected fish was 814.05 mg.h/L. Histological observations on the organs that play a role in the drug mechanism, to be specific on the liver, kidney, and intestine showed pathological abnormalities. Visualization of A. hydrophila by immunohistochemistry showed that bacteria were located in the lumen of blood vessels. The withdrawal time of oxytetracycline after 10 days of administration in uninfected and infected fish were 20 and 30 days, repectively. In conclusion, plasma levels of oxytetracycline in uninfected fish were greater than in infected fish and were followed by differences in other pharmacokinetic parameters and longer drug withdrawal times in infected fish.
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DOI: http://dx.doi.org/10.15578/jra.17.1.2022.47-57
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